tbuckley/cabot-search huggingface dataset:
Abstract 799: Measuring the impact of the COVID-19 pandemic on breast cancer screening in Puerto Rico
Authors: Vivian Colón-López, Hermilis Berrios Ortiz, Hector Contreras-Mora, Orville M. Disdier, Cynthia M. Pérez, Nilda Ríos, Olga L. Díaz, Juan Mejías, Erick L. Suárez-Pérez
Journal: Cancer Research (2023)

Abstract Introduction: The COVID-19 pandemic has caused major changes to healthcare services, especially those related to early detection and screening practices like breast cancer. In Puerto Rico, breast cancer is the main cause of death, representing 18.9% of cancer deaths in women, making early detection even more important to prevent morbidity and mortality. This study aims to describe the impact of COVID-19 on breast cancer screening and assess differences in health utilization by age group and health regions in Puerto Rico. Methods: This study used data on breast cancer screening medical claims from Puerto Rico Track, a project in collaboration with the Puerto Rico Public Health System and the Puerto Rico Institute of Statistics that aims to assess health access and utilization patterns in Puerto Rico. Claims including unilateral and bilateral mammography, sonommamography, and MRI were analyzed. Descriptive statistics and percentual changes between the COVID-19 baseline year (2016) compared with 2020 and 2021 were performed (overall, by age-group and health region). Results: A total of 193,793 screening tests were performed in 2016, compared to 66,463 in 2020, and 89,322 in 2021. Overall, a third of the medical claims for breast cancer screening (33.2%) were in the age group of 51-60 years. An overall decreasing percentual change was observed comparing 2016 vs. 2020 (65.7%), where the age group with the broadest gap reduction were among women 41-50 years old (68.2%). When comparing medical claims of 2016 (193,750) versus 2021 (89,320) (pre and post pandemic), an important decreasing change (53.9%) was observed. The age group with the highest decrease comparing 2016 to 2021 was the 41-50 years one (68.2%). The Western region of Mayagüez/Aguadilla had the highest decreasing percentual change, with a reduction of 73.6% in 2020 compared to 2016, and 62.6% when compared 2021 with 2016. Conclusion: Breast cancer screening was notably affected by the COVID-19 pandemic in Puerto Rico. A pattern of decreasing breast cancer screening was observed by health regions and by age. These efforts provide evidence of the need of tailored evidence-based interventions to increase breast cancer screening in the island. Citation Format: Vivian Colón-López, Hermilis Berrios Ortiz, Hector Contreras-Mora, Orville M. Disdier, Cynthia M. Pérez, Nilda Ríos, Olga L. Díaz, Juan Mejías, Erick L. Suárez-Pérez. Measuring the impact of the COVID-19 pandemic on breast cancer screening in Puerto Rico [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 799.
Abstract 861: Modelling the role of EGFR mutation in the initiation of never-smoker lung cancer
Authors: Helena M. Coggan, Clare E. Weeden, Mohit Dalwadi, Charles Swanton, Philip Pearce, Karen M. Page
Journal: Cancer Research (2023)

Abstract Genetic mutations associated with never-smoker lung cancer frequently appear in normal lung tissue, in both cancer and non-cancer patients. It is unclear what circumstances are required for a mutation to fix in healthy tissue and eventually lead to a tumor. To investigate this, alveolar type-II murine cells were grown in a 3D nutrient system, forming spheroidal clusters. The volumes of these clusters were measured at 7 and 14 days and a mathematical model was devised to describe their growth. In the absence of an EGFR mutation, variations in growth between clusters can be explained by a skew-normal distribution of initial division rates. These rates decline exponentially as the clusters age, and the decline rate is the same across clusters. When cells possess an epidermal growth factor receptor (EGFR) mutation or are grown in the presence of interleukin-1 beta (il-1b) growth factor, clusters form more complex shapes, which we believe may be driven by branching processes and cell-cell interactions. Accordingly, more complex models are needed to explain their development. This work lays the groundwork for new, parameterized models of mutational spread in lung tissue, and a deeper understanding of the role of mutation in carcinogenesis. Citation Format: Helena M. Coggan, Clare E. Weeden, Mohit Dalwadi, Charles Swanton, Philip Pearce, Karen M. Page. Modelling the role of EGFR mutation in the initiation of never-smoker lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 861.
Abstract 860: The dynamics of LINE-1 retrotransposition in cellular populations
Authors: Stephen Martis, Alexander Solovyov, Jayon Lihm, Hao Li, Benjamin Greenbaum
Journal: Cancer Research (2023)

Abstract Retrotransposons are genetic elements that have the ability to copy and paste themselves in the genome via the proteins they encode. Since the rapid growth of a retrotransposon can be highly deleterious at the organismal level, many of these genetic parasites are suppressed or have been inactivated over evolutionary time. However, the human genome still hosts the active retrotransposon LINE-1, whose aberrant expression is associated with various diseases, especially epithelial cancers. Despite these associations, a quantitative understanding of the dynamics and diversity of LINE-1 insertions in somatic tissue is lacking. In order to address this gap, we present a population dynamic model of LINE-1 retrotransposition in individual cells. Using the model, we show that at demographic equilibrium, the LINE-1 copy number distribution is broader than would be expected from classical population genetic models. We demonstrate how this broadening distorts the frequency spectrum of insertions. We compare the model's predictions to data from whole genome sequencing of individual tumor cells. Citation Format: Stephen Martis, Alexander Solovyov, Jayon Lihm, Hao Li, Benjamin Greenbaum. The dynamics of LINE-1 retrotransposition in cellular populations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 860.
Abstract 793: Mechanism of interferon induction by cannabidiol (CBD) and analogues in lung cancer cells
Authors: Leticia Stock, Lydia Robinson-Mailman, Long C. Nguyen, Shao-Nong Chen, Guido F. Pauli, Marsha R. Rosner
Journal: Cancer Research (2023)

Abstract CBD, an FDA approved drug for epilepsy, may have therapeutic potential for other diseases and is currently being tested for efficacy in cancer-related clinical trials. As the literature about CBD, especially in vitro reports, is often contradictory, increasing our understanding of its specific action on a molecular level will allow to determine whether CBD can become a useful therapy or exacerbates specific cancers in a context-dependent manner. Due to its relative lipophilicity, CBD is challenging to dispense at therapeutic concentrations; therefore, one goal is to identify cannabinoid congeners with greater efficacy and reduced drug delivery challenges. We recently showed that CBD activates interferons as a mechanism of inhibiting SARS-CoV-2 replication in lung carcinoma cells. As factors produced by the innate immune system, interferons have been implicated in both pro-survival and growth arrest and apoptosis signaling in cancer. Here we show that CBD induces interferon production and interferon stimulated genes (ISGs) through a mechanism involving NRF2 and MAVS in lung carcinoma cells. We also show that CBDV, which differs from CBD by 2 fewer aliphatic tail carbons, has limited potency, suggesting that CBD specifically interacts with one or more cellular proteins rather than having a non-specific effect. We also identified other CBD-related cannabinoids that are more effective at inducing ISGs. Taken together, these results characterize a novel mechanism by which CBD activates the innate immune system in lung cancer cells and identify related cannabinoids that have possible therapeutic potential in cancer treatment. Citation Format: Leticia Stock, Lydia Robinson-Mailman, Long C. Nguyen, Shao-Nong Chen, Guido F. Pauli, Marsha R. Rosner. Mechanism of interferon induction by cannabidiol (CBD) and analogues in lung cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 793.
Abstract 837: Preclinical development of ELU001: A folate receptor alpha (FRα)-targeted C’Dot drug conjugate (CDC) for the treatment of brain metastases
Authors: Gregory P. Adams, Tin Khor, Feng Chen, Kai Ma, Marion Scocca, Aranapakam Venkatesan, Cathy Reddick, Mary Hilgart, Thomas Gardinier, Fei Wu, Melik Turker, Peiming Chen, Vaibhav Patel, Eliel Bayever
Journal: Cancer Research (2023)

Abstract Antibody-drug conjugates (ADCs) exhibit limited efficacy against brain malignancies due to their inability to cross the blood-brain barrier (BBB) and penetrate into solid tumors. In clinical imaging studies C’Dots readily crossed tumor-disrupted BBB and penetrated across/localized in tumors in the brain avoiding healthy brain. CDCs are ultra-small (6-7 nm) nanoparticles with a silica core coated by short polyethylene glycol chains conjugated to up to 80 small payload and targeting moieties, creating highly potent and avid agents. CDCs’ small size mediates rapid renal clearance leading to limited exposure to healthy tissues. ELU001 is a potent anti-FRα CDC with an average of 21 exatecan topoisomerase-1 inhibitor payload molecules and 13 folic acid targeting molecules on its surface. ELU001 is currently in a dose escalation trial in patients with systemic solid tumor indications that have the potential to overexpress FRα. Early signs of activity with a manageable safety profile have been seen across antigen expression levels. ELU001 exhibits in vitro potency in the sub/low nanomolar range against cancer cell lines that express 3+, 2+ or 1+ levels of FRα. In studies performed in immunodeficient mice bearing intracranial NCI-H2228-luc bioluminescent non-small cell lung cancer tumors, ELU001 was observed to penetrate across disrupted BBB and localize in tumors. Microscopic analysis revealed that ELU001 distributed throughout the tumors but not into the healthy brain. Treatment with a single cycle of ELU001 Q3Dx3 in mice bearing either early (Day 7) or late (Day 14) brain tumors was well tolerated and resulted in significant reduction in tumor burden measured by bioluminescence as well as a prolonged survival benefit. Retreatment of these animals resulted in an additional decrease in tumor burden. These results suggest that ELU001 may have promise for the treatment of metastatic brain tumors that are difficult to treat with currently available agents. Citation Format: Gregory P. Adams, Tin Khor, Feng Chen, Kai Ma, Marion Scocca, Aranapakam Venkatesan, Cathy Reddick, Mary Hilgart, Thomas Gardinier, Fei Wu, Melik Turker, Peiming Chen, Vaibhav Patel, Eliel Bayever. Preclinical development of ELU001: A folate receptor alpha (FRα)-targeted C’Dot drug conjugate (CDC) for the treatment of brain metastases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 837.
Abstract 882: Functional enrichment analysis of somatic mutations identifies novel risk factors for pediatric neuroblastoma
Authors: Nolan D. Middleton, Eric Shelden
Journal: Cancer Research (2023)

Abstract Pediatric neuroblastoma is among the most common solid tumors in children and accounts for approximately 15% of childhood cancer mortalities. Neuroblastomas are highly heterogeneous cancers, and few common genetic alterations are currently associated with neuroblastoma tumorigenesis. Additionally, few genetic variations have been established as predictive factors for clinical outcomes in neuroblastoma cases. Here, a biological systems-level approach utilizing publicly-accessible data from the Genomic Data Commons was taken to identify genetic variations associated with altered survival times in neuroblastoma cases. Two survival analyses of clinical neuroblastoma cases were conducted: one associated with genetic variations in individual somatic genes and the other associated with groups of mutations identified using functional enrichment analysis. Mutations in only two individual genes displayed significant associations with altered survival: ALK (ALK receptor tyrosine kinase), a known hallmark of neuroblastoma, and DNAH17 (dynein axonemal heavy chain 17). In contrast, patient cohorts established by functional enrichment analysis of mutated genes identified 148 biological systems where somatic gene variations were significantly associated with altered survival. Gene sets defined by the function of their products in ALK signaling, as well as alteration in cells treated with Crizotinib, an inhibitor of receptor tyrosine kinases including ALK, both displayed highly significant association with altered survival. Of the 148 systems identified, 128 others lacked any association with ALK. Of these, eight showed a more significant association with altered survival than the ALK signaling pathway itself. These results identify novel risk factors associated with reduced survival in pediatric neuroblastoma patients and illustrate the potential of systems-level analysis to generate insight into the biology of heterogeneous cancers. Citation Format: Nolan D. Middleton, Eric Shelden. Functional enrichment analysis of somatic mutations identifies novel risk factors for pediatric neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 882.
Abstract 84: Single-cell transcriptional analysis of multiple myeloma bone marrow aspirates using particle-templated instant partition sequencing (PIPseq)
Authors: Yonatan Katzenelenbogen, Mor Zada, Robert Meltzer, Kristina Fontanez, Ido Amit
Journal: Cancer Research (2023)

Abstract Single-cell RNA-seq technologies have dramatically evolved in recent years. Despite these advances, the field faces some significant limitations in the versatility of current single cell technologies. These limitations include speed, ease of use, and the ability to sample both vast and minimal numbers of cells in a single batch - particularly in human samples. The PIPseq approach is based on Particle-templated Instant Partitions (PIPs) that allow single-cell encapsulation and barcoding using uniform droplet emulsions with minimal lab hardware. PIPseq is particularly effective for routine, high-throughput analysis of multiple myeloma bone marrow biopsies. Patients with multiple myeloma undergo a series of treatments aimed at depleting their malignant plasma cells (PC). Nevertheless, a high rate of relapse is observed despite low PC levels detected in the bone marrow (BM). Deep molecular profiling of the cellular pathways of rare PC, as well as their unique microenvironment, may shed light on the mechanisms underlying resistance to conventional therapies. As part of an ongoing clinical research, a bone marrow sample from a patient with multiple myeloma was molecularly characterized using the PIPseq T2 3’ Single Cell RNA Kit. Two distinct cell populations from a frozen BM biopsy were sorted into the T2 PIPseq tube: CD45+ cells (tumor microenvironment; TME) and rare malignant PC. In spite of the limited number of cells in the biopsy, PIPseq analysis clearly resolved both the malignant PC and the TME, demonstrating its utility for extensive analyses of fresh or frozen clinical myeloma samples. Citation Format: Yonatan Katzenelenbogen, Mor Zada, Robert Meltzer, Kristina Fontanez, Ido Amit. Single-cell transcriptional analysis of multiple myeloma bone marrow aspirates using particle-templated instant partition sequencing (PIPseq) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 84.
Abstract 2250: Immuno-oncology study to profile the tumor microenvironment in multiple human cancers using high-plex imaging mass cytometry
Authors: Thomas D. Pfister, Liang Lim, Shaida Ouladan, Nick Zabinyakov, Qanber Raza, Christina Loh
Journal: Cancer Research (2023)

Abstract Immune profiling of tumor tissues has become a key tool in understanding the complexity of the tumor microenvironment (TME), for predictive biomarker discovery, and in cancer treatment. The presence of tumor-infiltrating lymphocytes has been associated with benefit from therapy. Furthermore, the TME also contains immunosuppressive elements that can impede immune response. Imaging Mass Cytometry™ (IMC™) enables detailed assessment of cell phenotype and function using 40-plus markers simultaneously at subcellular resolution on a single slide without spectral overlap or background autofluorescence. High-plex IMC has enabled us to evaluate the TME in different cancer histologies including in highly autofluorescent tissue types like lung, hepatocellular carcinoma, and skin melanoma. The Maxpar® Human Immuno-Oncology IMC Panel Kit (201508) was customized using antibodies from the Standard BioTools™ catalog to create panels for tissue-based immuno-oncology research. Data acquisition was performed using a Hyperion™ Imaging System. To facilitate cell segmentation, an IMC Cell Segmentation Kit (TIS-00001) was applied to enhance cell membrane boundaries. We applied a pixel classification approach and CellProfiler™ for single-cell segmentation. We used histoCAT™ for single-cell analysis to visualize protein expression in various cancer types via PhenoGraph clustering and t-SNE maps. Our panels were applied to normal and cancer human tissue microarrays (TMAs) to phenotype and analyze cell populations in these tissues. We provide detailed analysis of the TME by classifying activation state of immune cell populations, epithelial-to-mesenchymal transition (EMT) progression, and composition of the extracellular matrix. In-depth single-cell analysis quantitatively evaluated the cellular makeup and immune cell component in the TME of cancer tissues and identified major tumor, immune, and stromal cell phenotypes. This work demonstrates the capability of IMC for quantitative and spatial identification of multiple immune parameters in the TME on a single slide of cancer patient samples (e.g. tumor microarray). For Research Use Only. Not for use in diagnostic procedures. Citation Format: Thomas D. Pfister, Liang Lim, Shaida Ouladan, Nick Zabinyakov, Qanber Raza, Christina Loh. Immuno-oncology study to profile the tumor microenvironment in multiple human cancers using high-plex imaging mass cytometry [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2250.
Abstract 1346: Phagocytosis of solid tumors favors macrophage clusters and cooperativity in tumor elimination
Authors: Dennis E. Discher
Journal: Cancer Research (2023)

Abstract Macrophages are abundant in many solid tumors and are potential effector cells for monoclonal antibody-based immunotherapies because they can in principle phagocytose IgG-opsonized cancer cells. However, it remains unknown whether phagocytic macrophages can overcome the cohesive forces between cancer cells in solid tumors. We show that maximum phagocytosis of B16 melanoma tumors and ‘tumoroids’ requires IgG-opsonization and very deep suppression of the macrophage checkpoint ligand CD47. Under these conditions, phagocytic macrophages cluster or ‘phase separate’, and the elimination exhibits clear cooperativity with respect to macrophage number and phagocytic activity. In vitro disruption of phagocytic clusters specifically implicates Mg2+ and macrophage integrins. Cytokine treatments and other inhibitors further implicate roles for integrins and phagocytic surface receptors. Although tumor-associated macrophages correlate with negative prognoses in many cancers, our findings are among the first to reveal advantages of high macrophage numbers, macrophage clusters, and resulting cooperative effects when combined with opsonizing antibodies and CD47 disruption. Lastly, the challenging B16 tumors are durably eliminated by the approach and induce de novo IgG's that also drive anti-cancer phagocytosis. Citation Format: Dennis E. Discher. Phagocytosis of solid tumors favors macrophage clusters and cooperativity in tumor elimination [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1346.